宫颈疾病病理《生殖系统和乳腺疾病》课件

生殖系统和乳腺疾病

Diseasesofgenitalsystemandmammarygland

Hereisanormalcervixwithasmooth,glisteningmucosalsurface.Thecervicalosissmallandround,typicalforanulliparouswoman.Theoswillhaveafish-mouthshapeafteroneormorepregnancies.Thenormaladultvaginalmucosawithawrinkledappearance.Thecervixhasbeenopenedtorevealanendocervicalcanalleadingtotheloweruterinesegmentattherightthathasanerythematousappearanceextendingtothecervicalosconsistentwithchronicinflammation.Theyellowdashedlinemarkstheouterboundaryofthetransformationzone.Outsidetheboundarythelong-establishedandthickstratifiedsquamousepitheliumappearswhiteorlightpinkfollowingthediluteacidtreatment.Insidetheboundary,thetransformationzoneischaracterizedbyareasofthinepithelium,whichappearredoralmostinflamed.

1.生育期妇女最常见

2.多继发于分娩、流产等→子宫颈损伤

3.临床:白带过多

一、慢性子宫颈炎(Chroniccervicitis)

常见感染:链球菌、肠球菌、大肠杆菌、葡萄球菌等

特殊感染:沙眼衣原体、淋球菌、病毒

(单纯疱疹病毒、人乳头状瘤病毒、巨细胞病毒等)、结核菌、寄生虫及放线菌等Etiology肉眼：宫颈粘膜充血、肿胀，颗粒状或糜烂状Pathologicalchanges

子宫颈粘膜充血水肿间质单核C、淋巴C、浆C浸润子宫颈柱状上皮、腺上皮增生或鳞状化生

子宫颈息肉(cervicalpolyp)

有时子宫颈囊肿

(纳博特囊肿,Nabothiancyst)镜下：Thisisnormalcervicalnon-keratinizingsquamousepithelium.Thesquamouscellsshowmaturationfrombasallayertosurface.Thisischroniccervicitisatthesquamo-columnarjunctionofthecervix.Smallrounddarklymphocytesareseeninthesubmucosa,andthereisalsohemorrhage.Squamousmetaplasiaofcervix

CervicalpolypNabothiancystInthecervix,koilocytoticchangewithhumanpapillomavirus(HPV)infection,withvacuolizationofepithelialcells.

子宫颈糜烂

假性糜烂-柱状上皮代替鳞状上皮，多见

真性糜烂-鳞状上皮坏死脱落

Cervicalerosionoccurswhenthesurfaceofthecervixisreplacedwithinflamedtissuefromthecervicalcanal.Theconditionmaybecausedbytrauma,infectionorchemicals.二、子宫颈上皮非典型增生和原位癌

子宫颈上皮非典型增生－癌前病变异型细胞增生，从基底层向表层发展

原位癌上皮全层为异型细胞所替代，未突破基底膜

好发部位：子宫颈鳞-柱上皮交界带

(移行带)(Cervicalepithelialdysplasiaandcarcinomainsitu)异型细胞：类似正常基底细胞或体积较小，大小不等，细胞排列紊乱，可见核分裂。Ⅰ级（轻度）→异型细胞限于上皮下1/3↓（CINⅠ）多数可消退Ⅱ级（中度）→异型细胞累及上皮下2/3↓（CINⅡ）Ⅲ级（重度）→异型细胞超过上皮2/3以上↓（CINⅢ）原位癌

→上皮全层细胞异型，极性消失，但基底膜完整↓（CINⅢ）原位癌累及腺体（仍为原位癌）↓浸润癌→突破基底膜，向上皮下浸润扩展

重度非典型增生和原位癌没有明显界限，原位癌的异型细胞多形性更显著，核分裂多见。子宫颈上皮内瘤变

(Cervicalintraepithelialneoplasia,CIN)2014版WHO分类：宫颈鳞状上皮前驱病变细胞学与组织学采用相同的诊断术语，共同的临床处理方案低级别鳞状上皮内病变（LSIL）CINI（VaIN1）、扁平湿疣、尖锐湿疣ICD-O:/0观察随访、避免过度治疗高级别鳞状上皮内病变（HSIL）CINII-III（VaINII-III)ICD-O:/2手术治疗Cervicalintraepithelialneoplasia(CIN-1and-2)Cervicalintraepithelialneoplasia(CIN-3)Cervicalintraepithelialneoplasia(CIN-3)CervicalcarcinomainsituCervicalcarcinomainsituwithglands

轻度非典型增生:多数可自然消退

<2%→浸润癌非典型增生→

原位癌约10年

>20%

CINⅢ

→浸润癌10年内非典型增生+16、18或33型HPV感染→较高恶变倾向检查手段：碘液实验、脱落细胞学、组织病检

Prognosis三、子宫颈癌1.女性高发恶性肿瘤之一，开展普查→晚期癌↓，5年生存率和治愈率↑2.40-60岁高发3.临床:阴道不规则流血、接触性出血、白带↑

(Carcinomaofthecervix)

*

与早婚、多产、性生活紊乱、子宫颈裂

伤、包皮垢、感染等因素有关*通常继发于CIN

*与人类乳头状瘤病毒(HPV)16、18型，其次

31、33型的感染有关Etiology组织来源子宫颈阴道部或移行带：鳞状上皮子宫颈管粘膜柱状上皮柱状上皮下的储备细胞大体分型：糜烂型外生菜花型内生浸润型溃疡型Pathologicalchanges1.子宫颈鳞状细胞癌：占90%

早期浸润癌（微小浸润型鳞状细胞癌）浸润癌少数肿瘤细胞突破基底膜浸润间质的深度不超过基底膜下5mm没有血管浸润也无淋巴结转移常无明显临床症状癌组织突破基底膜明显浸润间质，深度超过基底膜下5mm伴有临床症状者组织分型高分化鳞癌(20%):

癌巢、角化珠,核分裂不多镜下:中分化鳞癌

(60%):无明显角化和癌珠形成，不规则和条型癌巢,核分裂和细胞异型性较明显低分化磷癌(20%):细胞呈小梭形，似基底细胞，异型性及核分裂都很明显，对放射线最敏感，但预后较差2.子宫颈腺癌：占10-25%

Alargeprotrudingmassisseenincervicalcanalextendingtothefornixofvagina.Adenocarcinomainsitu

Poorlydifferentiatedadenocarcinoma

直接蔓延:膀胱、直肠、盆腔、阴道、宫体淋巴道转移:

最常见，子宫旁→闭孔、髂内、髂外、髂总、腹股沟、骶前Ln，晚期锁骨上Ln

血道转移:肺、胃、肝SpreadingandmetastasisThisisalargercervicalsquamouscellcarcinomawhichspreadtothevagina.Thisisanotherpelvicexenterationforcervicalsquamouscellcarcinoma.Theirregulargrey-browntumorextendstowardbladderandupintotheuterus.Invasivesquamouscarcinomaofcervixinvascularchannel.Thepresenceoftumorcellswithinthelumenofacapillary-likespaceisevidenceforaggressivegrowthpotentialinsquamouscarcinomaofthecervixandhasbeencorrelatedwithincreasedriskforregionallymphnodemetastasis.1.不规则阴道流血、接触性出血2.白带增多3.腰骶部疼痛4.子宫膀胱瘘/子宫直肠瘘5.定期脱落细胞检查－早期发现Clinicalrelations临床分期：0期:原位癌I期:局限于子宫颈内Ⅱ期:侵及盆腔和阴道Ⅲ期:侵及盆腔壁和阴道下1/3Ⅳ期:侵出骨盆,累及膀胱粘膜或直肠四.子宫平滑肌瘤

Leiomyomaoftheuterus1.最常见2.≥30岁,70%3.多无症状，出血，尿频，不孕，自然流产，绝经后萎缩4.遗传倾向PathologicalchangesAlarge,solitaryleiomyoma.AsubmucosalleiomyomaMultiplesubmucosal,intramural,andsubserosalleiomyomasoftheuterus.

Reddegeneration生长部位：子宫肌层、子宫浆膜下或子宫内膜下单发或多发：多者达数十个大小悬殊：小者仅镜下可见，大者>30cm形态：球形或不规则形，界清，无包膜切面观：灰白，质韧，编织状或旋涡状继发性改变：玻璃样变、粘液变、囊性变、钙化、出血及坏死等大体：与正常子宫平滑肌细胞相似瘤细胞-

核排列较密集束状或编织状排列核长杆状，两端钝圆，染色质纤细

镜下:Uterineleiomyomaisabenignconnectivetissuetumorofthesmoothmusclecellsofthemyometrium.Tumorcellsresemblenormalcells(elongated,spindle-shaped,withacigar-shapednucleus)andformbundleswithdifferentdirections(whirled).Thetumoriswellcircumscribed,butnotencapsulated.

良、恶性之间的区别取决于三个标准：

分裂像

细胞异型性坏死肿瘤核分裂像10个/10HP，有细胞异型性及坏死者为恶性

子宫平滑肌肉瘤

（Leiomyosarcoma）Thisisaleiomyosarcomaprotrudingfrommyometriumintotheendometrialcavityofthisuterus.Muchmorecellularandthecellshavemuchmorepleomorphismandhyperchromatismthanthebenignleiomyoma.Anirregularmitosisisseeninthecenter.子宫体癌(子宫内膜腺癌)

（Endometrialadenocarcinoma）1.发病率上升2.绝经期、绝经后妇女，50-59岁3不规则阴道流血4.生长缓慢,转移较晚5.一般与雌激素长期作用有关肉眼：局部型：多见，多位于子宫底或子宫角，息肉状、乳头状弥漫型：内膜弥漫性增厚，灰白质脆，伴出血、坏死、溃疡Pathologicalchanges

镜下：高分化：多见，腺管排列拥挤、紊乱，轻度异型，似增生的内膜腺体中分化：腺体不规则，排列紊乱，乳头或筛状，异型明显，核分裂易见低分化：实体片状，无腺样结构，异型明显，核分裂多见Theendometrialadenocarcinomainthepolypattheleftismoderatelydifferentiated,asaglandularstructurecanstillbediscerned.Notethehyperchromatismandpleomorphismofthecells,comparedtotheunderlyingendometriumwithcysticatrophyattheright.

Adenocarcinoma,endometrium,uterus,welldifferentiated.Thetallcolumnarepitheliumandwell-definedglandformationillustrateawell-differentiatedadenocarcinoma.Thisisendometrialadenocarcinomawhichcanbeseeninvadingintothesmoothmusclebundlesofthemyometrialwalloftheuterus.Welldifferentiatedadenocarcinomahasinvadedthroughthemusclebundlesofthemyometrium(redarrow).Theadenocarcinomaisindicatedbytheredarrows.

腺棘皮癌：分化较好的腺癌中有良性化生的鳞状上皮腺鳞癌：腺癌组织中混杂鳞癌上皮直接蔓延：

上－子宫角，输卵管、卵巢下－宫颈管和阴道外－浆膜、腹膜和大网膜淋巴道：

宫底－腹主动脉旁Ln

子宫角－腹股沟Ln

宫颈－宫旁、髂内外、髂总Ln血道：肺、肝、骨骼Spreadingandmetastasis临床分期：Ⅰ期:局限于宫体,5年生存率90%Ⅱ期:累及子宫体和子宫颈,30-50%Ⅲ期:侵入盆腔Ⅳ期:侵出盆腔,累及膀胱和直肠

张三，女，58岁，五年前绝经，近一月来出现阴道不规则流血，B超发现子宫底部见一菜花状肿物，病理活检见灰白色质脆组织，显微镜下腺体排列拥挤、紊乱，细胞有明显异型性。病理诊断：?

Casediscuss子宫内膜腺癌

乳腺癌

Carcinomaofbreast

Anormalductcells

Bbasementmembrane

Clumen(centerofduct)导管双层上皮内腺上皮，外肌上皮Normallobuleofmammarygland全球每年120万妇女患乳腺癌，50万死于该病北美、北欧高我国↑3%/年，“第一癌症杀手”40-60岁女性，男性罕见1%乳腺外上象限>中央区>内上象限

来自乳腺终末导管小叶单元上皮IntroductionER、PR(+)：内分泌治疗好，预后好C-erbB-2(+),ER(-):预后差乳腺是女性激素的靶器官正常乳腺上皮细胞存在雌激素受体（ER）

孕激素受体（PR）ER、PR→启动细胞分裂→促乳癌生长Thecellsofthisbreastcarcinomaarehighlypositiveforestrogenreceptorwiththisimmunoperoxidasestain.Estrogenreceptorpositivitycorrelateswithabetterprognosis.Thisisprogesteronereceptor(PR)positivityinabreastcarcinoma.Theusefulnessofthisdeterminationisnotaswellestablishedasforestrogenreceptors.CarcinomasthatarePRpositive,butnotERpositive,mayhaveaworseprognosis.分类：乳腺癌非浸润性癌

浸润性癌导管内原位癌小叶原位癌粉刺癌非粉刺导管内癌Paget病浸润性导管癌浸润性小叶癌特殊类型癌小管癌典型髓样癌粘液癌

属于原位癌

没有突破导管和腺泡的基底膜分类:导管内原位癌

小叶原位癌

一、非浸润性癌1．导管内原位癌

（Intraductalcarcinomainsitu）

起于乳腺小叶的终末导管限于导管内,基膜完整检出率↑，5%－15%－30%

组织学:粉刺型,非粉刺型

20年，30%－浸润癌AnormalductcellsBductalcancercellsCbasementmembraneDlumen(centerofduct)Intraductalcarcinoma.Theneoplasticcellsareconfinedtotheductbythebasementmembrane.Theneoplasticcellsaremonotonouswithroundtoovalnucleiandlittlepleomorphism.Thecellbordersarewelldemarcated.

（1）粉刺癌（Comedocarcinoma）

>50%位于乳腺中央部质硬、肿块明显，易触诊查出导管扩张，内含坏死物质挤压导管,坏死物质会像粉刺一样被挤出

镜下:实性排列，中央坏死－特征癌细胞大，嗜酸，大小不一，核仁明显，病理性核分裂多坏死区常见钙化导管周间质纤维组织↑，慢性炎C浸润Comedocarcinomaischaracterizedbythepresenceofrapidlyproliferating,high-grademalignantcells.Thecellsinthecenteroftheductsareoftennecroticandcalcify.Thiscentralnecrosisleadstothegrosscharacteristicofextrusionofcheesymaterialfromtheductswithpressure.

ComedocarcinomaNotecentralnecrosis(*)andpleomorphicnuclei.Thecellsdonotextendbeyondthebasementmembrane(arrow).Thecenteroftheductcontainscalcifiedmaterialsurroundedbynecrotic,mostlyacellular

debris.Theneoplasticcellsexhibitnuclearpleomorphismandhyperchromasia.Thebasementmembraneisintact(2)非粉刺型导管内癌（Noncomedointraductalcarcinoma）实性、乳头状、筛状排列，轻微坏死癌细胞小，较规则导管周间质纤维组织增生较轻2.小叶原位癌（Lobularcarcinomainsitu）

来自小叶的终末导管及腺泡

癌细胞局限于管泡内，未穿破其基底膜，小叶结构存在

多中心性，常累及双侧，无明显肿块癌细胞实性排列，小而一致，核圆，核分裂罕见癌细胞无坏死，无间质的炎症反应、纤维组织增生

AnormallobularcellsBlobularcancercellsCbasementmembraneLobularcarcinomainsituconsistsofaneoplasticproliferationofcellsintheterminalbreastductsandacini.Thecellsaresmallandround.Thereisa30%riskfordevelopmentofinvasivecarcinomainthesameortheoppositebreast.导管内癌－－乳头、乳晕乳头、乳晕可见渗出、浅表溃疡又称“湿疹样癌”表皮内：瘤细胞孤立散在、成簇分布

大而异型，胞质透明3.佩吉特病（Pagetdisease)癌细胞穿破乳腺导管或腺泡的基底膜而侵入间质占乳腺癌>85%分类：浸润性导管癌和浸润性小叶癌两种类型可并存，占10%，浸润性小叶癌的预后较差

二、浸润性癌导管内癌细胞突破管壁基底膜向间质浸润最常见（70%）1.浸润性导管癌（Invasiveductalcarcinoma）

AnormalductcellsBductalcancercellsbreakingthroughthebasementmembraneCbasementmembrane大体：色灰白，质硬，无包膜界不清，活动度差侵润性生长乳头下陷，橘皮样外观PathologicalchangesHereisaclassicinfiltratingductalcarcinomaThisinfiltratingductalcarcinomaofthebreastisdefinitelyinfiltratingthesurroundingbreast.Thecentralwhiteareaisveryhardandgritty,becausetheneoplasmisproducingadesmoplasticreactionwithlotsofcollagen.Thisisoftencalleda"scirrhous"appearance.镜下：巢状、团索状、腺样，可见导管内原位癌癌细胞异型明显，核分裂多伴坏死、纤维组织增生单纯癌、硬癌、不典型髓样癌Cordsandnestsofcellsirregularlyinvadethetissue.Reactivefiborsis(thedesmoplasticreaction)surroundstumorcells(arrows).Inthecenterisaductlinedbycarcinomacells.However,thisductalcarcinomaisnotconfinedtojusttheduct,butinfiltratesoutwardintothesurroundingstromaasaninfiltratingductalcarcinomaThepleomorphismofthecarcinomacellswithintheductinthecenter(inacribriformpattern),aswellastheneoplasticcellsinfiltratingthroughthestromaandfat,canbeseenwiththisinfiltratingductalcarcinoma.Theinfiltratingductalcarcinomaofbreasthaspleomorphiccellsinfiltratingthroughthestroma.Thebluearrowssurroundanestofneoplasticcellsinaninfiltratingductalcarcinoma.Thegreenarrowheadspointtointerveningstroma.Mitoticfiguresareseen.Small,duct-likestructuresareseeninvadingthebreaststroma.Sometumorcellsaresingle.Notetheabundantcollagenousstroma,characteristicofbreastcarcinomas.Scirrhouscarcinomaofthebreast

5%～10%，老年妇女多见癌细胞突破基底膜向间质浸润约20%可累及双侧乳房，弥漫性多灶性分布，不易发现2.浸润性小叶癌（Invasivelobularcarcinoma）AnormalcellsBlobularcancercellsbreakingthroughthebasementmembraneCbasementmembrane

*橡皮样，灰白柔韧，边界不清*

转移特殊性：脑脊液、浆膜面、卵巢、子宫、骨髓肉眼：

串珠状、细条索或环形排列正常导管周围癌细胞小、大小一致、核分裂象少见镜下：Thisisacloserviewoflineararraysoflobularcarcinomacellsinfiltratingthroughdensefibrousstroma.InvasivelobularcarcinomaTheneoplastic

cellsarenotableforeccentricnucleisetintomucinrichcytoplasm.Thenucleiarehyperchromaticandroundtooval.Nopleomorphismormitosesareseen.Thestromaisverydensewithaccellularcollagen.Singlestrandsofmalignantcellsinfiltratingthestroma(Indianfiling).3.特殊型癌

具有特殊形态，如粘液癌、大汗腺样癌、腺样囊性癌、鳞状细胞癌、炎性癌

直接浸润：乳腺实质、乳头、皮肤、筋膜、胸肌及胸壁

淋巴结转移：

外上、外下象限和中心区→同侧腋窝淋巴结

内上、内下象限→乳内动脉旁淋巴结

血行转移：远处任何器官

转移途径135影响预后的因素

早期不易发现，发现时约50%病例已有局部淋巴结转移

原发灶大小：<1cm、无LN转移者预后好

淋巴结转移：无LV转移者5年生存率70-80%

组织学类型：

组织学分级：腺管的分化程度、细胞异型性、核分裂

ER和PR：内分泌治疗、预后

HER-2：靶向药物Herceptin、预后

DNA倍体数：

新辅助化疗：乳腺癌的分子分型Nature

2000;406,

747–752乳腺癌Her-2靶向治疗乳腺纤维腺瘤Fibroadenomaofbreast

最常见的良性肿瘤20-30岁多见单个或多个，单侧或双侧发生界清，切片灰白、质韧、可见裂隙状，粘液

样外观乳腺增生性病变Proliferativelesionsofbreast

乳腺纤维囊性变Fibrocysticchangesofbreast硬化性腺病Sclerosingadenosis乳腺纤维囊性变一组非肿瘤性病变，以末梢导管、腺泡扩张，间质纤维组织和上皮不同程度增生为特点25-45